Proliferative vitreoretinopathy (PVR) is a leading cause of failure or retinal detachment surgery. In PVR, foreign cells invade the vitreous and proliferate in that compartment. Although cells of retinal origin are involved in this pathology, it is not known which cells are pivotal and what agents stimulate the foreign tissue growth. A long term objective is to identify the combination of cells and growth promoters that potentiate PVR so that specific methods can be devised to interfere with undesirable proliferation. The aims of this application are (1) to determine if human vitreous contains proliferation stimulants for ocular cells and if levels of stimulants correlate with PVR severity, and (2) to investigate the growth properties of retinal glial cells, cells that may be central to the pathology because they increase proliferation by cell-cell association. To achieve the first goal, ocular cells (glia, pigment epithelium, scleral fibroblasts) will be exposed to vitreal samples retrieved from patients at vitrectomy in a quantifiable assay for cell proliferation to determine if the human vitreous contains cell type-specific mitogens. Vitreal mitogenicity will be correlated with the patient's clinical condition. To achieve the second goal, co-cultures of glial cells with other ocular cells (pigment epithelium, scleral fibroblasts) will be tested for the reciprocal induction of DNA synthesis in a radioautographic assay in which both cell populations can be assessed. Co-cultures will also be exposed to vitreal samples to determine if mixed cell populations are more responsive to vitreal stimulants. Mixed cultures showing an elevated growth rate in vitro will also be injected into the rabbit vitreous in an experimental model of PVR to determine if mixed vitreal membranes promote more severe pathology than membranes derived from a single cell population.